Zoonotic and emerging infectious diseases represent an increasing and very real threat to global health, and it is essential that we expand our understanding of the pathogenesis and prevention of these diseases because of the increasing density of human populations, the increased exposure to domestic animal populations, and the crowding of wildlife into limited areas with frequent human contact. To address the growing need for infectious disease research, a COBRE Center of Excellence was established at MSU, with the goal of positioning Montana as a national leader in research on zoonotic infectious diseases. Over the past 9 years, the Center has been extremely successful, resulting in infrastructure development (facilities & equipment), recruitment and support of junior investigators (7 COBRE Projects, 6 new hires, and 20 Pilot Projects), and formation of a cohesive Center of investigators. The synergism of these components has resulted in the establishment of a solid foundation for infectious disease research in the region. Importantly, these efforts have fostered faculty career development and have created a pipeline of new researchers with interest and expertise in infectious disease pathogenesis. With this solid infrastructure foundation in place, we are now ideally poised for Center transition to a sustainable research enterprise. Our long term goal is to maintain a sustainable Center of Excellence that is focused on understanding the mechanisms of pathogenesis, host immune response, and immunotherapeutic development for zoonotic and emerging infectious diseases of regional and worldwide importance. The primary goal of COBRE III is to facilitate transition of the Center into a sustainable entity with state-of-the-art research core facilities and a vibrant research environment. Through COBRE III efforts, we also seek to maintain and enhance the critical mass of investigators needed to support future program initiatives. While the foundation and infrastructure for achieving these goals have been established during COBRE l/ll, there is still a critical need for infrastructure optimization and acquisition of additional researchers in he area of infectious diseases to enrich the group and facilitate programmatic efforts. The transition to Center sustainability will be stimulated by an enhanced Pilot Grants Program that will expand the scope and impact of Center research and increase the number of collaborative efforts leading toward larger program-type grants. Likewise, the transition to Center sustainability will involve solidfying scientific Core structure and optimizing utilization of Core research facilities/resources. Finally, Center transition will be enhanced by career development initiatives such as educational programs and mentoring activities, to meet the needs of all Center associated investigators. Importantly, this Center will continue to be highly interactive and collaborative and will play an important role in expanding the infectious disease research enterprise in Montana.